Insmed Incorporated (Nasdaq:INSM) today announced additional results
from the Company’s phase 2 clinical trial of ARIKAYCETM, or
liposomal amikacin for inhalation, for the treatment of patients with
treatment resistant nontuberculous mycobacterial (NTM) lung infections.
The results are highlighted in a poster entitled, “A Randomized,
Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for
Inhalation (ARIKAYCE) in Patients with Recalcitrant Nontuberculous
Mycobacterial Lung Disease,” that will be presented today at the
American Thoracic Society’s Annual Meeting 2014 in San Diego, California
by Kenneth N. Olivier, M.D., M.Ph., National Institute of Allergy and
Infectious Diseases and a co-Principal Investigator of the study. The
poster is available on the Company’s website at www.insmed.com.
At the conclusion of the 84-day double blind phase of the trial, 78 of
the 80 patients agreed to receive once-daily ARIKAYCE plus standard of
care treatment for an additional 84 days. Data from 68 of these patients
who completed the visits during the additional open label phase were
available for inclusion in the poster. These results collected from the
open label phase show that 21 of these patients were culture negative
for NTM at Day 168. This data reflects 10 patients who were culture
negative at Day 84 as well as 5 additional patients from the ARIKAYCE
arm and 6 additional patients who were on placebo, switching to ARIKAYCE
during the open-label phase. The number of patients with negative
cultures increased from the double blind phase of the trial in which 11
out of 44 patients treated with ARIKAYCE (added to standard of care
treatment) demonstrated negative cultures by day 84 of the study as
compared to 3 out of 45 patients treated with standard of care plus
placebo.
“We are encouraged by these additional and durable culture conversions
which we believe is the ultimate goal in the treatment of NTM lung
infections,” said Will Lewis, President and Chief Executive Officer of
Insmed. “The patients screened for admission to this trial are
recalcitrant to treatment. While the entry criteria for this trial
required a minimum of 6 months on standard of care therapy, over 75% of
patients entering this trial were treated with standard of care therapy
for more than a year, yet remained culture positive. In addition, a
majority of these patients suffer from at least one additional pulmonary
co-morbidity, such as bronchiectasis or cystic fibrosis, making the
hurdle quite high for showing any improvement and making these results
that much more encouraging for patients suffering from this disease. We
now look forward to the regulatory discussions in the United States and
Europe that will guide our path forward.”
In the next several months, the Company plans to incorporate the trial
results into discussions with the regulatory agencies in the United
States and Europe to determine next steps for ARIKAYCE in the treatment
of NTM lung infections. Based upon the culture conversion results, in
April 2014 the Company applied for Breakthrough Therapy Designation for
ARIKAYCE in the United States. ARIKAYCE has already received Orphan
Drug, Qualified Infectious Disease Product (QIDP) and Fast Track
designations from the U.S. Food and Drug Administration (FDA) for the
treatment of NTM lung infections and recently received Orphan Drug
Designation from the European Medicines Agency (EMA).
Clinical Trial Design and Key Endpoints
The randomized, double-blind, placebo-controlled phase 2 clinical trial
compared ARIKAYCE (590 mg delivered once daily for 84 days), added to
standard of care treatment, versus standard of care treatment plus
placebo, in 89 adult patients with treatment resistant NTM lung disease
at 19 sites in North America. Eligibility for the study required
patients to have been on the American Thoracic Society/Infectious
Diseases Society of America (ATS/IDSA) guidelines-based therapy for at
least six months prior to screening with persistently positive
mycobacterial cultures. Following the randomized portion of the study,
all eligible patients had the option to receive ARIKAYCE once daily for
an additional 84 days in an open-label design.
The primary efficacy endpoint of the study was a semi-quantitative
measurement of the change in mycobacterial density on a seven-point
scale from baseline (Day 1) to the end of the randomized portion of the
trial (Day 84). ARIKAYCE did not meet the pre-specified level for
statistical significance although there was a positive trend (p=0.148)
in favor of ARIKAYCE. The key secondary endpoint of culture conversion
reached statistical significance in favor of ARIKAYCE.
Safety
Patients receiving ARIKAYCE experienced adverse events consistent with
those seen in similar patient populations receiving inhaled antibiotics.
Overall, mild to moderate upper respiratory irritation was more common
in the ARIKAYCE arm compared to the placebo arm and there was no
difference in severe serious adverse reactions or hemoptysis between the
two arms. There was one Suspected Unexpected Serious Adverse Reaction
(SUSAR) observed in the double-blind phase and one SUSAR observed in the
open-label phase. Instances of hearing loss or tinnitus, a side effect
more commonly associated with intravenous dosing of amikacin, were
evenly balanced between the ARIKAYCE and placebo arms.
About Nontuberculous Mycobacteria (NTM)
Nontuberculous mycobacteria (NTM) are organisms found in the soil and
water that can cause serious lung disease in susceptible individuals,
for which there are currently limited effective treatments and no
approved therapies. The prevalence of NTM disease is reported to be
increasing, and according to reports from the American Thoracic Society
is believed to be greater than that of tuberculosis in the U.S.
According to the National Center for Biotechnology Information,
epidemiological studies show that presence of NTM infection is
increasing in developing countries, perhaps because of the
implementation of tap water. Women with characteristic phenotype are
believed to be at higher risk of acquiring NTM infection along with
patients with defects on cystic fibrosis transmembrane conductance
regulators.
NTM lung disease is often a chronic condition that can lead to
progressive inflammation and lung damage, and is characterized by
bronchiectasis and cavitary disease. NTM infections often require
lengthy hospital stays for medical management. Treatment usually
involves multi-drug regimens that can be poorly tolerated and have
limited effectiveness, especially in patients with severe disease or in
those who have failed prior treatment attempts. According to a
company-sponsored patient chart study conducted by Clarity Pharma
Research, approximately 50,000 patients suffering from NTM lung disease
visited physician offices in the U.S. during 2011.
About ARIKAYCE™
ARIKAYCE is a form of the antibiotic amikacin, which is enclosed in
nanocapsules of lipid called liposomes. This advanced pulmonary liposome
technology prolongs the release of amikacin in the lungs while
minimizing systemic exposure. The treatment uses biocompatible lipids
endogenous to the lung that are formulated into small (0.3 micron),
charge-neutral liposomes. ARIKAYCE is administered once-daily using an
optimized, investigational eFlow® Nebulizer System manufactured by PARI
Pharma GmbH, a novel, highly efficient and portable aerosol delivery
system.
This is the first controlled clinical trial of an antibiotic in patients
suffering from NTM lung infections. There are no drugs approved by the
FDA for the treatment of this chronic, debilitating disease.
About eFlow® Technology and PARI Pharma
ARIKAYCE is delivered by an investigational eFlow® Nebulizer
System developed by PARI Pharma and optimized specifically for ARIKAYCE.
The optimized device uses eFlow Technology to enable highly efficient
aerosolization of medication including liposomal formulations via a
vibrating, perforated membrane that includes thousands of laser-drilled
holes. Compared with other nebulization technologies, eFlow Technology
produces aerosols with a very high density of active drug, a precisely
defined droplet size and a high proportion of respirable droplets
delivered in the shortest possible period of time. eFlow Technology is
not an ultrasonic nebulizer technology and is not a general purpose
electronic aerosol generator nebulizer technology. Combined with its
quiet mode of operation, small size, light weight and battery use, eFlow
Technology reduces the burden of taking daily, inhaled treatments.
About Insmed
Insmed Incorporated is a biopharmaceutical company dedicated to
improving the lives of patients battling serious lung diseases. Insmed
is focused on the development and commercialization of ARIKAYCE, or
liposomal amikacin for inhalation, for at least two identified orphan
patient populations: patients with nontuberculous mycobacteria (NTM)
lung infections and cystic fibrosis (CF) patients with Pseudomonas
aeruginosa lung infections. For more information, please visit http://www.insmed.com.
Forward-looking Statements
This release contains forward-looking statements. Words, and variations
of words, such as “intend,” “expect,” “will,” “anticipate,” “believe,”
“continue,” “propose” and similar expressions are intended to identify
forward-looking statements. Investors are cautioned that such statements
in this release, including statements relating to the status, results
and timing of clinical trials and clinical data, the anticipated
benefits of Insmed’s products, the anticipated timing of regulatory
submissions, and the ability to obtain required regulatory approvals,
bring products to market and successfully commercialize products
constitute forward-looking statements that involve risks and
uncertainties that could cause actual results to differ materially from
those in the forward-looking statements. Such risks and uncertainties
include, without limitation, failure or delay of European, Canadian,
U.S. Food and Drug Administration and other regulatory reviews and
approvals, competitive developments affecting the Company’s product
candidates, delays in product development or clinical trials or other
studies, patent disputes and other intellectual property developments
relating to the Company’s product candidates, unexpected regulatory
actions, delays or requests, the failure of clinical trials or other
studies or results of clinical trials or other studies that do not meet
expectations, the fact that subsequent analyses of clinical trial or
study data may lead to different (including less favorable)
interpretations of trial or study results or may identify important
implications of a trial or study that are not reflected in Company’s
prior disclosures, and the fact that trial or study results or
subsequent analyses may be subject to differing interpretations by
regulatory agencies, the inability to successfully develop the Company’s
product candidates or receive necessary regulatory approvals, the
ability to obtain Breakthrough Therapy Designation for ARIKAYCE in the
U.S., the inability to make product candidates commercially successful,
changes in anticipated expenses, changes in the Company’s financing
requirements or ability to raise additional capital, and other risks and
challenges detailed in the Company’s filings with the U.S. Securities
and Exchange Commission, including, without limitation, its Annual
Report on Form 10-K for the year ended December 31, 2013 and its
subsequent quarterly reports on Form 10-Q. Investors are cautioned not
to place undue reliance on any forward-looking statements that speak
only as of the date of this news release. The Company undertakes no
obligation to update these forward-looking statements to reflect events
or circumstances or changes in its expectations.
Copyright Business Wire 2014